Effects of male sex hormone on the plasma lipoprotein metabolism and CETP expression in sedentary and trained genetically modified mice

Author(s)

Andrea Camargo Casquero

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2005-06-27

Examining board members

Helena Coutinho Franco de Oliveira; Eliana Cotta de Faria; Maria Cristina Cintra Gomes Marcondes; Edna Regina Nakandakare; Bruno Geloneze Neto

• Advisor: Helena Coutinho Franco de Oliveira

Abstract

Gender differences in lipoprotein profile and atherosclerotic disease risk are generally attributed to an attenuating effect of estrogen and/or to a proatherogenic action of androgens. In this work we studied the effects of dificiency and excess of testosterone on the lipoprotein metabolism and development of atherosclerosis in transgenic mice expressing CETP with or without partial deficiency of the LDL receptor. In the first study, we showed that testosterone deficiency increased the levels of plasma LDL-cholesterol, and the titers of auto-antibodies anti-oxidized LDL and doubled the size of atherosclerotic lesions in the aortic roots. CETP expression in this animal model led to a less pronounced elevation of LDL-cholesterol and reduced significantly the atherosclerotic lesion size. In the second study, we compared the effects of two types of testosterone supplementation, metabolizable or not. We showed that either type of testosterone induced significant elevations in LDL- and HDL- cholesterol. Howerver, only the metabolizable testosterone promoted an increase in the CETP and a reduction in the hepatic lipase expression. In the third work, we investigated the interaction between the effects of non metabolizable testosterone (mesterolone) and physical exercise. We observed that the physical exercise increased HDL, more potently in animals expressing CETP and without mesterolone treatment. Physical exercise also reduced the CETP activity, triglycerides and free fatty acids levels, independently of the mesterolone treatment. The treatment with mesterolone increased VLDL, independently of the genotype and physical active state, and reduced HDL in the exercised mice (AU)